The long-term goal of this proposal is to investigate the mechanism involved in B cell activation. Previous studies have shown that Fc fragments obtained by papain digestion of IgG proteins induce a marked proliferative response in B cells. Furthermore, the Fc fragments have both a positive and a negative regulatory effect on the in vitro antibody response. Our proposed studies have been designed to link this biological activity of the Fc fragments with their ability to bind to lymphocytes and to determine if the receptors binding immune complexes on B cells are the same as those involved in their proliferative response to Fc fragments. Since preliminary studies have shown that antigen-antibody complexes also cause a proliferative response by mouse spleen cells, both the nature of the complexes that are effective and the cell types involved will be determined. The binding and stimulatory effects of immune complexes and Fc fragments will be compared simultaneously, the ontogeny of these two, quite separate activities will be traced. A comprehensive study on the regulation of in vitro antibody responses by both Fc fragments and antigen-antibody complexes will be initiated. In experiments with the in vitro secondary response, particular attention will be given to the immune status of donor spleen cells, since preliminary experiments suggest that this status determines whether enhancement or suppression occurs. The optimal ratio of antigen; antibody required for either a positive or negative regulation will be determined. In the case of both the primary and secondary in vitro response the cell type(s) involved in regulation will be assessed. Special attention will be given to the way in which both suppressor T cells and macrophages participate. Although T cells do not proliferate in response to Fc fragments, their possible amplifying effect on B cell activation by Fc fragments will be tested.